Archives for Chemistry Experiments of 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex

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Nickel and palladium complexes with the 1,1′-bis(diphenylphosphino)ferrocene ligand effectively catalyze regioselective cross-coupling of allylic ethers such as 1- or 3-methyl-2-propenyl silyl ethers with aryl-Grinard reagents, where the nickel catalyst leads to carbon-carbon bond formation at the more substituted posiiton while carbon-carbon bond formation occurs at the less substituted position in the case of the palladium catalyst.Allylation of cis- and trans-5-methyl-2-cyclohexenyl silyl ethers was found to proceed with inversion of configuration with both the nickel and palladium catalysts.The stoichiometric reaction of a (1-methyl-?-allyl)palladium complex with the phenyl-Grinard reagent in the presence of phosphine ligands was also studied.A mechanism involving formation of the ?-allyl(aryl)ML2 intermediate is proposed.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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(Chemical Equation Presented) A total synthesis of the complex, bent aromatic ring-containing marine alkaloid haouamine A is achieved through a route in which every step (with the exception of the final deprotection) is performed on a gram-scale. This is accomplished through the development of a method for the dehydrogenation of cyclohexenones that allows for point-to-planar chirality transfer. This strategy makes it possible to program the desired atropisomeric outcome from a simple chiral cyclohexenone. By synthesizing atrop-haouamine A, this work has firmly established that natural haouamine exists as a single, nonequilibrating atropisomer. Finally, biological investigations demonstrate that the bent aromatic ring of this natural product is critical for anticancer activity against PC3 cells.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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In the search for light-addressable nanosized compounds we have synthesized 10 dinuclear homometallic trisbipyridyl complexes of linear structure with the general formula [M(bpy)3-BL-M(bpy)3]4+ [M = Ru(II) or Os(II); BL = polyphenylenes (2, 3, 4, or 5 units) or indenofluorene; bpy = 2,2?-bipyridine]. By using a “chemistry on the complex” approach, different sizes of rodlike systems have been obtained with a length of 19.8 and 32.5 A for the shortest and longest complex, respectively. For one of the ruthenium precursors, [RUbpy-ph2-Si(CH3) 3][PF6]2, single crystals were obtained by recrystallization from methanol. Their photophysical and electrochemical properties are reported. All the compounds are luminescent both at room and low temperature with long excited-state lifetimes due to an extended delocalization. Nanosecond transient absorption showed that the lowest excited state involves the chelating unit attached to the bridging ligand. Electrochemical data indicated that the first reduction is at a slightly more positive potential than for the reference complexes [M(bpy)3]2+ (M = Ru, Os). This result confirms that the best acceptor is the bipyridine moiety connected to the conjugated spacers. The role of the tilt angle between the phenylene units, in the two series of complexes, for the ground and excited states is discussed.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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wherein Ar, R1, R2 and n have the meanings indicated in the claims. The compounds of the formula I are valuable pharmacologically active compounds which modulate protein kinase activity, specifically the activity of serum and glucocorticoid regulated kinase (SGK), in particular of serum and glucocorticoid regulated kinase isoform 1 (SGK-1, SGK1),and are suitable for the treatment of diseases in which SGK activity is inappropriate, for example degenerative joint disorders or inflammatory processes such as osteoarthritis or rheumatism. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use as pharmaceuticals, and pharmaceutical compositions comprising them

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The involvement of the phosphoinositide 3-kinases (PI3Ks) in several diseases, especially in the oncology area, has singled it as one of the most explored therapeutic targets in the last two decades. Many different inhibitor classes have been developed by the industry and academia with a diverse selectivity profile within the PI3K family. In the present manuscript we report a further exploration of our lead PI3K inhibitor ETP-46321 (Martinez Gonzalez et al., 2012)1 by the application of a conformational restriction strategy. For that purpose we have successfully synthesized novel tricyclic imidazo[1,2-a]pyrazine derivatives as PI3K inhibitors. This new class of compounds had enable the exploration of the solvent-accessible region within PI3K and resulted in the identification of molecule 8q with the best selectivity PI3Kalpha/delta isoform profile in vitro, and promising in vivo PK data.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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A new strategy was developed for intercepting the palladium-alkyl species generated in Heck reaction via nucleophilic addition prior to the step of migratory insertion, which leads to a new palladium-catalyzed difunctionalization of enol ethers with aminals and alcohols to afford amino acetals. Mechanistic studies suggested that the cationic cyclometalated Pd(II) complex generated by the oxidative addition of aminal to a Pd(0) species was crucial for this unusual transformation.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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In breast cancer, estrogen receptor alpha (ERalpha) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERalpha positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochemical properties. We describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs. This article culminates in the identification of LSZ102 (10), a compound in clinical development for the treatment of ERalpha positive breast cancer.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Fused tricyclic compounds, methods of using such compounds in the treatment of hormone sensitive diseases such as prostate cancer, and pharmaceutical compositions containing such compounds.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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ortho-Arylthio triarylbismuthanes [2-(Ar?S)C6H 4]nBiAr3-n have been conveniently synthesized by insertion of benzyne into the bismuth-sulfur bond of (Ar?S) nBiAr3-n (n = 1, 2). A similar insertion takes place when a homologous antimony congener is used, but no reaction is observed with its phosphorus analogue. This suggests a clear difference in the bond strength between pnictogen-sulfur bonds. The carbon-bismuth bond of [2-(2-BrC 6H4S)C6H4]nBiAr 3-n undergoes Pd-catalyzed intramolecular cross-coupling to produce dibenzothiophene in good yield. An X-ray crystallographic study of 2-(2-BrC 6H4S)C6H4BiTol2 (Tol = 4-MeC6H4) reveals that this molecule is present in a dimeric structure, where the six heteroatoms including bismuth, sulfur, and bromine are linked through the nonbonded intramolecular bismuth-sulfur and intermolecular sulfur-bromine and bromine-bromine interactions.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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The present invention provides agents effective to treat eye diseases, pharmaceutical compositions comprising them, methods for preparing pharmaceuticals for treatment of eye diseases comprising using the agents, use of the agents in manufacture of pharmaceuticals for treatment of eye diseases and methods for treating eye diseases comprising administering the agents or the pharmaceutical compositions. The eye diseases treated by the present invention include particularly glaucoma, especially normal tension glaucoma, or retinitis pigmentosa. The present invention provides the compound of formula (I) wherein R is as defined in the description.

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Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method